ACTIVATION PROPERTIES OF CHEMICALLY SKINNED FIBERS FROM HUMAN ISOLATED BRONCHIAL SMOOTH-MUSCLE

1. The contractile activation properties of human isolated bronchial smooth muscle were investigated using chemically (beta-escin) skinned strips. 2. Concentration-dependent contractions were induced by free ion concentrations of Ca2+ (0.5-3 mu M), Sr2+ (2-200 mu M) and Ba2+ (50-1000 mu M). The resulting -log[cation]-tension relationships were fitted by sigmoidal curves with EC(50) values (cation concentration required to produce half-maximal tension) and co-operativity factors (Hill coefficient, n(H)) of, respectively, 0.25 mu M and 3.4 for Ca2+, 12 mu M and 2.64 for Sr2+ and 100 mu M and 1.73 for Ba2+. Maximal responses to Sr2+ and Ba2+ were 125.5 +/- 15.4 and 96 +/- 8.1% (n=5) respectively of the maximum tension induced by Ca2+. 3. Trifluoperazine (5-100 mu M), cyclic BMP (50-300 mu M) and cyclic GMP (50-100 mu M) each antagonized Ca2+ in a concentration-dependent manner. On the other hand, okadaic acid (OA, 0.2-1 mu M) potentiated Ca2+ and increased the maximum response to Ca2+ (+25 +/- 5.4 %, n = 5, for 1 mu M OA). 4. This study has demonstrated the high Ca2+ sensitivity of the activation mechanism of human isolated bronchial smooth muscle. It also suggests that control of the contractile machinery in the human bronchus involves processes of phosphorylation and dephosphorylation. The beta-escin-treated human bronchus may be a useful model for investigating the cellular basis of some pathophysiological processes such as bronchial hyper-responsiveness.